FIGURE 7.

P-gp maturation is highly sensitive to point mutations at the second transmission interface but relatively insensitive to changes at the first transmission interface. Predicted structure of human P-gp in an open conformation (based on the crystal structure of mouse P-gp) (56). Mutation of residues in ICL2 and ICL3 inhibited maturation of P-gp. The side chains of these residues are shown in blue and red, respectively. None of the mutations in ICLs 1 and 4 inhibited maturation of P-gp and their side chains are shown in green.